Gamma protocadherins are required for survival of spinal interneurons

Xiaozhong Wang, Joshua A. Weiner, Sabine Levi, Ann Marie Craig, Allan Bradley, Joshua R. Sanes*

*Corresponding author for this work

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

The murine genome contains ∼70 protocadherin (Pcdh) genes. Many are expressed in the nervous system, suggesting that Pcdhs may specify neuronal connectivity. Here, we analyze the 22 contiguous genes of the Pcdh-γ cluster. Individual neurons express subsets of Pcdh-γ genes. Pcdh-γ proteins are present in most neurons and associated with, but not confined to, synapses. Early steps in neuronal migration, axon outgrowth, and synapse formation proceed in mutant mice lacking all 22 Pcdh-γ genes. At late embryonic stages, however, dramatic neurodegeneration leads to neonatal death. In mutant spinal cord, many interneurons are lost, but sensory and motor neurons are relatively spared. In cultures from mutant spinal cord, neurons differentiate and form synapses but then die. Thus, Pcdh-γ genes are dispensable for at least some aspects of connectivity but required for survival of specific neuronal types.

Original languageEnglish (US)
Pages (from-to)843-854
Number of pages12
JournalNeuron
Volume36
Issue number5
DOIs
StatePublished - Dec 5 2002

ASJC Scopus subject areas

  • Neuroscience(all)

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